The mechanisms and regulation of DNA replication and cell division in E. coli will be examined by studying autonomous plasmid replication, and the division cycle of dnaA mutants growing under integrative suppression. The studies on autonomous plasmid replication are designed to determine: 1) the timing of replication of various F' plasmids during the chromosome-division cycle of three substrains of E. coli B/r growing at a variety of rates, 2) alterations in initiation of chromosome replication and the lengths of the C and D periods due to the presence of large, autonomously replicating plasmids, and 3) the requirements for RNA synthesis, protein synthesis, cell mass, initiation or termination of chromosome replication, and the dnaA and dnaC gene products for initiation of rounds of F' plasmid replication. The studies on the dnaA mutants growing at non-permissive temperature due to suppressive integration by F' plasmids are designed to determine aspects of the coupling between chromosome replication and cell division. The experiments will determine: 1) the sequence and rate of chromosome replication, 2) cell ages at initiation of chromosome replication, 3) the lengths of the C and D periods and the relationship between chromosome termination and initiation of cell division, and 4) the requirements for RNA and protein synthesis for chromosome replication and cell division during integrative suppression.